Inhibiting the compensatory elevation of xCT collaborates with disulfiram/copper-induced GSH consumption for cascade ferroptosis and cuproptosis

Zhang, Ping; Zhou, Chaoting; Ren, Xueying; Jing, Qiangan; Gao, Yan; Yang, Chen; Shen, Yuhuan; Zhou, Yi; Hu, Wanye; Jin, Feifan; Xu, Haifeng; Yu, Lingyan; Liu, Yingchao; Tong, Xiangmin; Li, Yanchun; Wang, Ying; Du, Jing

doi:10.1016/j.redox.2023.103007

Cited by 13 publications

(2 citation statements)

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“…This effect is coupled with GSH depletion, heightened lipid peroxides, and a compensatory increase in solute carrier family 7 member 11 and activated expression of ATF4, thereby inducing both ferroptosis and cuproptosis. 43 , 201 Moreover, the encapsulation of DSF in nanoparticles or liposomes has been reported to augment its therapeutic effects. 202 , 203 Currently, studies on copper ionophores in CRC mainly focused on DSF and ES, and other copper ionophores need to be further explored to enhance their therapeutic effect on CRC.…”

Section: Role Of Copper In the Treatment And Diagnosis Of Crcmentioning

confidence: 99%

Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies

Wang,

Pei,

Yang

et al. 2024

Clinical & Translational Med

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Copper, a trace element and vital cofactor, plays a crucial role in the maintenance of biological functions. Recent evidence has established significant correlations between copper levels, cancer development and metastasis. The strong redox‐active properties of copper offer both benefits and disadvantages to cancer cells. The intestinal tract, which is primarily responsible for copper uptake and regulation, may suffer from an imbalance in copper homeostasis. Colorectal cancer (CRC) is the most prevalent primary cancer of the intestinal tract and is an aggressive malignant disease with limited therapeutic options. Current research is primarily focused on the relationship between copper and CRC. Innovative concepts, such as cuproplasia and cuproptosis, are being explored to understand copper‐related cellular proliferation and death. Cuproplasia is the regulation of cell proliferation that is mediated by both enzymatic and nonenzymatic copper‐modulated activities. Whereas, cuproptosis refers to cell death induced by excess copper via promoting the abnormal oligomerisation of lipoylated proteins within the tricarboxylic acid cycle, as well as by diminishing the levels of iron‐sulphur cluster proteins. A comprehensive understanding of copper‐related cellular proliferation and death mechanisms offers new avenues for CRC treatment. In this review, we summarise the evolving molecular mechanisms, ranging from abnormal intracellular copper concentrations to the copper‐related proteins that are being discovered, and discuss the role of copper in the pathogenesis, progression and potential therapies for CRC. Understanding the relationship between copper and CRC will help provide a comprehensive theoretical foundation for innovative treatment strategies in CRC management.

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Section: Role Of Copper In the Treatment And Diagnosis Of Crcmentioning

confidence: 99%

Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies

Wang,

Pei,

Yang

et al. 2024

Clinical & Translational Med

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“…Chen et al reported that the Hinokitiol Cu complex (HK-Cu) induced striking accumulation of ubiquitinated proteins on A549 and K562 cancer cells, and caused cell death by inhibiting the activity of the 19S proteasomal deubiquitinase (DUB) [ 35 ]. Furthermore, the authors of [ 36 ] reported that Cu ionophores such as disulfiram/Cu induced ferroptosis and cuproptosis in hepatocellular carcinoma cells, accompanied by a reduction in GSH, an increase in lipid peroxides and a compensatory increase in the solute carrier family 7 member 11, by inhibiting the degradation mediated by the ubiquitin–proteasome. We may say, then, that Cu stabilizes ubiquitinated proteins by interfering with the UPS upstream, thus causing the accumulation of ubiquitinated proteins and implicating the UPS in the cuproptosis process.…”

Section: Cu Homeostasis and Cuproptosis Mechanismmentioning

confidence: 99%

The Molecular Mechanisms of Cuproptosis and Small-Molecule Drug Design in Diabetes Mellitus

Pan,

Huang,

Gan

et al. 2024

Molecules

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In the field of human health research, the homeostasis of copper (Cu) is receiving increased attention due to its connection to pathological conditions, including diabetes mellitus (DM). Recent studies have demonstrated that proteins associated with Cu homeostasis, such as ATOX1, FDX1, ATP7A, ATPB, SLC31A1, p53, and UPS, also contribute to DM. Cuproptosis, characterized by Cu homeostasis dysregulation and Cu overload, has been found to cause the oligomerization of lipoylated proteins in mitochondria, loss of iron–sulfur protein, depletion of glutathione, production of reactive oxygen species, and cell death. Further research into how cuproptosis affects DM is essential to uncover its mechanism of action and identify effective interventions. In this article, we review the molecular mechanism of Cu homeostasis and the role of cuproptosis in the pathogenesis of DM. The study of small-molecule drugs that affect these proteins offers the possibility of moving from symptomatic treatment to treating the underlying causes of DM.

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Ferroptosis mechanisms and its novel potential therapeutic targets for DLBCL

Bian,

Li,

Chen

et al. 2024

Biomedicine & Pharmacotherapy

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Inhibiting the compensatory elevation of xCT collaborates with disulfiram/copper-induced GSH consumption for cascade ferroptosis and cuproptosis

Cited by 13 publications

References 73 publications

Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies

Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies

The Molecular Mechanisms of Cuproptosis and Small-Molecule Drug Design in Diabetes Mellitus

Ferroptosis mechanisms and its novel potential therapeutic targets for DLBCL

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